Pyrrole-2-carboxylic ester

As in the furan series, the loss of an OH or an -OR group is very favored in pyrrole carboxylic acids and esters, (53)->[51]. The presence of an N—H group in a-pyrrole carboxylic esters causes also the elimination of an ROH fragment,41 (53)->[54]. 

Substituted indoles are of biological interest and are not readily synthesized by conventional methods of indole chemistry. Annulation of a nuclear methyl and an a-ethoxyimine (or an imidate) under basic conditions is a promising procedure. The pyridine oxide ester (87.1) may be converted in high yields into two kinds of pyrrole carboxylic ester the potassium salt of the imidate, on heating in DMF, gives the 3-(2-oxocarboxylate) whereas dilute mineral acid leads to the 2-carboxylate ester. 

Birch reduction of pyrrole carboxylic esters and tertiary amides gives dihydro-derivatives the presence of an electron-withdrawing gronp on the nitrogen serves both to remove the acidic iV-hydrogen and also to rednce the electron density on the ring. Quenching the immediate reduced species - an enolate - with an alkyl halide produces alkylated dihydropyrroles. ... 

Unsymmetrically substituted dipyrromethanes are obtained from n-unsubstitued pyrroles and fl(-(bromomethyl)pyiToIes in hot acetic acid within a few minutes. These reaction conditions are relatively mild and the o-unsubstituted pyrrole may even bear an electron withdrawing carboxylic ester function. It is still sufficiently nucleophilic to substitute bromine or acetoxy groups on an a-pyrrolic methyl group. Hetero atoms in this position are extremely reactive leaving groups since the a-pyrrolylmethenium( = azafulvenium ) cation formed as an intermediate is highly resonance-stabilized. 

Other Methods. Newer methods for forming pyrrole and related heterocyctic rings iaclude the formatioa of substituted pyrrole 2-carboxylate esters by coadeasatioa of P-dicarboayl compouads with glyciaate esters (25). 

Pyrrole Carboxylic Acids and Esters. The acids are considerably less stable than benzoic acid and often decarboxylate readily on heating. However, electron-withdrawing substituents tend to stabilize them toward decarboxylation. The pyrrole esters are important synthetically because they stabilize the ring and may also act as protecting groups. Thus, the esters can be utilized synthetically and then hydrolyzed to the acid, which can be decarboxylated by heating. Often P-esters are hydrolyzed more easily than the a-esters. 

Selective oxidation of methyl pyrroles 65 possessing an a-carboxylic ester and sensitive p-substituents can be accomplished using cerium triflate in methanol <96TL315>. Moreover, the resultant a-methoxymethylpyrroles 66 may be converted to dipyrrylmethanes 67 in a "one-pot" sequence by treatment with 48% HBr. The dipyrrylmethanes, in turn, can be further oxidized to dipyrryl ketones by ceric ammonium nitrate <96JHC221>. 

As in carboxylic esters it is possible to substitute alkoxy groups of Fischer-type carbene complexes by non-carbon nucleophiles, such as other alcohols [73,214,218], enols [219], aliphatic amines [43,64,66,220-224], aniline [79], imines [225], or pyrroles [226]. Strong nucleophiles can also lead to a dealkylation of methoxy-substituted carbene complexes (5 2 at the methyl group, [227]), in the same way as methyl esters can be cleaved by nucleophiles such as iodide. Carbon... 

The presence of a carboxylic ester at position 5 of a pyrimidine ring contributes to a series of fused pyrroles containing a carbonyl group (Equation 86). The pyrimidine 240a is heated at reflux with cyclohexylamine for 8h providing 241a <2001JHC1051>. 

Furans, thiophenes, thiazoles and pyrroles all reacted smoothly with alkylydenecyclopropanes in the presence of a palladium catalyst and added tributylphosphone, to give the allylated heterocycles as product. Thus furane-2-carboxylic ester on treatment with the butyl substituted alkylydenecyclopropane gave the 5-allyl-2-furanecarboxylate in good yield (6.96.).128... 

Figure 16 Principal mass spectrometric fragmentations for pyrrole carboxylic acids and esters...

Predictably, nitrosation of 2-acetylpyrrole and pyrrole-2-carboxylic esters with alkyl nitrites or nitrous acid preferentially yields the relatively stable 4-nitroso derivatives, whilst 2,4-dialkyl- or -diaryl-pyrroles are nitrosated at the 5-position. Further reaction of the dialkyl and diaryl nitrosopyrroles with an excess of alkyl nitrite in the absence of a base can result in the formation of the nitropyrroles, whereas the reaction with nitrous acid converts the nitrosopyrroles into diazopyrroles (B-77MI30502). 

The apparent abnormal formation of ethyl pyrrole-2-carboxylate from the reaction of ethyl chloroformate and alkali metal salts of pyrrole could be accounted for by a thermal rearrangement during the isolation of the products. However, whilst this may be partly correct, an analysis of the reaction products prior to their isolation has established (77CJC4103) the formation of the thermodynamically more stable 2-carboxylic ester from the 1-isomer by a reaction sequence shown in Scheme 36. 

Halogenomethylpyrroles have been oxidized with lead(IV) salts or by chromium trioxide to yield the formylpyrroles, whilst catalytic hydrogenolysis or zinc-acetic acid reduction produces the 2-methylpyrroles (B-77MI30504). The methyl derivatives are also obtained by hydride reduction of trifluoromethyl-pyrroles and -indoles, and trifluoromethylindoles are converted into the carboxylic esters by ethanol under basic conditions (74JOC1836). 

The reverse reactivity is noted in the acid-catalyzed hydrolysis of the esters. Pyrrole-3-carboxylic esters are hydrolyzed upon dissolution in concentrated sulfuric acid and subsequent dilution with ice. Evidence has been presented indicating that unimolecular acyl—O fission forms the resonance-stabilized pyrrolyl acylium ion (B-77MI30505). 

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